During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis ...(CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.
Spasticity is a complex and often disabling symptom for patients with upper motor neuron syndromes. Although spasticity arises from neurological disease, it often cascades into muscle and soft tissue ...changes, which may exacerbate symptoms and further hamper function. Effective management therefore hinges on early recognition and treatment. To this end, the definition of spasticity has expanded over time to more accurately reflect the spectrum of symptoms experienced by persons with this disorder.
Once identified, clinical and research quantitative assessments of spasticity are hindered by the uniqueness of presentations both for individuals and for specific neurological diagnoses. Objective measures in isolation often fail to reflect the complex functional impact of spasticity. Multiple tools exist to quantitatively or qualitatively assess the severity of spasticity, including clinician and patient‐reported measures as well as electrodiagnostic, mechanical, and ultrasound measures. A combination of objective and patient‐reported outcomes is likely required to better reflect the burden of spasticity symptoms in an individual.
Therapeutic options exist for the treatment of spasticity along a broad spectrum from nonpharmacologic to interventional procedures. Treatment strategies may include exercise, physical agent modalities, oral medications, injections, pumps, and surgery. Optimal spasticity management most often requires a multimodal approach, combining pharmacological management with interventions that match the functional needs, goals, and preferences of the patient. Physicians and other healthcare providers who manage spasticity must be familiarized with the full array of spasticity interventions and must frequently reassess results of treatment to ensure the patient's goals of treatment are met.
Background
Along with COVID‐19 pandemic, India has faced an outbreak of COVID‐19–associated mucormycosis (CAM). Due to restricted availability of amphotericin B during this outbreak, clinicians were ...forced to use posaconazole or isavuconazole preparations as first‐line or alternate therapy in many patients. We planned an early monitoring of posaconazole trough level while using delayed release (DR) tablet as first‐line or alternate therapy.
Objectives
Primary objective of the study was to determine percentage of patients achieving arbitrarily decided therapeutic posaconazole levels (≥1.2 μg/ml) after using standard dosages of posaconazole. Secondary objective was to identify potential factors associated with sub‐therapeutic posaconazole levels.
Methods
We performed retrospective chart review of the hospitalised patients, who received posaconazole DR tablet as first‐line or alternate therapy to treat CAM during outbreak period (March 1 to May 31, 2021). High‐performance liquid chromatographic (HPLC) method was used to measure trough level of posaconazole.
Results
Posaconazole serum levels of 29 patients were analysed, who received posaconazole DR tablet. Majority (n = 23) were male with the median (range) age 53 (24–86) years. The mean (SD) posaconazole level was 1.66 (0.76) μg/ml. Sub‐therapeutic posaconazole trough level was observed in 7 (24.1%) patients. Relatively younger patients were associated with lower posaconazole level (p = .046). Except two patients, all the patients tolerated posaconazole well.
Conclusions
The study supports the posaconazole trough level measurement on day 4 while using posaconazole DR tablet as first‐line or alternate therapy to treat mucormycosis during limited supply of amphotericin B.
Cervical dystonia (CD) is primarily treated with botulinum toxin, at intervals of ≥ 12 weeks. We present efficacy, patient-reported outcomes (PROs), and safety in adults with CD at the last available ...visit after a single set of abobotulinumtoxinA (aboBoNT-A) injections versus placebo using 500 U in a 2-mL injection volume. In this 12-week, randomized, double-blind trial, patients were ≥ 18 years of age with primary idiopathic CD, had a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥ 20, and TWSTRS-Severity subscale score > 10 at baseline. Patients (N = 134) were randomized (2:1) to aboBoNT-A (n = 89) or placebo (n = 45), with aboBoNT-A patients treated with 500 units (U) if toxin-naïve, and 250 to 500 U based on previous onabotulinumtoxinA dose if non-naïve. Endpoints included total TWSTRS, Pain Numeric Rating Scale (NRS-Pain; 24-hour), Treatment Satisfaction Questionnaire for Medication, and other PROs for pain, depression, and global health. Results are for the intent-to-treat population, with "Week 12" (Wk12) comprising the last available post-baseline assessment (end-of-study or early withdrawal). Mean TWSTRS total scores improved from 42.5 at baseline to 35.4 at Wk12 with aboBoNT-A and 42.4 to 40.4 with placebo (treatment difference: -4.8; 95% confidence interval CI: -8.5, -1.1; p = 0.011). At Wk12, mean (95% CI) change from baseline in NRS-Pain was -1.0 (-1.59, -0.45) for aboBoNT-A and -0.2 (-0.96, 0.65) for placebo. AboBoNT-A demonstrated numeric improvements in other PROs. More aboBoNT-A-treated patients than patients receiving placebo reported being at least "somewhat satisfied" with treatment (60.4% vs 42.2%, respectively), symptom relief (57.0% vs 40.0%), and time for treatment to work (55.8% vs 33.3%). No new adverse events were reported. Results indicate that in patients with CD, treatment with aboBoNT-A using a 2-mL injection provided sustained improvement in the TWSTRS total score and patient-perceived benefits up to 12 weeks. Trial registration: Clinicaltrials.gov Identified: NCT01753310.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic had led to an increase in a surge of mucormycosis in COVID-19 patients, especially in India. Diabetes and irrational usage of corticosteroids ...to treat COVID-19 were some of the factors implicated for COVID-19-associated mucormycosis (CAM). We designed this case-control study to identify risk factors for mucormycosis in COVID-19 patients. The study was conducted at a private tertiary care center in western India. Data were extracted from records of COVID 19 patients (January–May 2021) and divided into two groups: Those with proven or probable mucormycosis, and those without mucormycosis with a ratio of 1:3. A binary logistic regression analysis was done to assess potential risk factors for CAM. A total of 64 CAM and 205 controls were included in the analysis. Age and sex distribution were similar in cases and controls with the majority of males in both the groups (69.9%) and the mean age was 56.4 (±13.5) years. We compared the comorbidities and treatment received during acute COVID-19, specifically the place of admission, pharmacotherapy (steroids, tocilizumab, remdesivir), and the requirement of oxygen as a risk factor for CAM. In a multivariate analysis, risk factors associated with increased odds of CAM were new-onset diabetes (vs. non-diabetics, adjusted odds ratio OR 48.66, 95% confidence interval CI 14.3–166), pre-existing diabetes (vs. non-diabetics, aOR 2.93, 95%CI 1.4–6.1), corticosteroid therapy (aOR 3.64, 95%CI 1.2–10.9) and home isolation (vs. ward admission, aOR 4.8, 95%CI 2–11.3). Diabetes, especially new-onset, along with corticosteroid usage and home isolation were the predominant risk factors for CAM.
Lay Summary
This study revealed new-onset diabetes, pre-existing diabetes, corticosteroid therapy, and home isolation as risk factors for COVID-19-associated mucormycosis. Avoiding the use of corticosteroids in non-severe COVID-19 disease coupled with proper blood sugar monitoring and control will help to reduce the CAM burden.
The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of ...incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.
Purpose
A systematic epidemiological study on intensive care unit (ICU)-acquired candidemia across India.
Method
A prospective, nationwide, multicentric, observational study was conducted at 27 ...Indian ICUs. Consecutive patients who acquired candidemia after ICU admission were enrolled during April 2011 through September 2012. Clinical and laboratory variables of these patients were recorded. The present study is an analysis of data specific for adult patients.
Results
Among 1,400 ICU-acquired candidemia cases (overall incidence of 6.51 cases/1,000 ICU admission), 65.2 % were adult. Though the study confirmed the already known risk factors for candidemia, the acquisition occurred early after admission to ICU (median 8 days; interquartile range 4–15 days), even infecting patients with lower APACHE II score at admission (median 17.0; mean ± SD 17.2 ± 5.9; interquartile range 14–20). The important finding of the study was the vast spectrum of agents (31
Candida
species) causing candidemia and a high rate of isolation of
Candida tropicalis
(41.6 %). Azole and multidrug resistance were seen in 11.8 and 1.9 % of isolates. Public sector hospitals reported a significantly higher presence of the relatively resistant
C. auris
(8.2 vs. 3.9 %;
p
= 0.008) and
C. rugosa
(5.6 vs. 1.5 %;
p
= 0.001). The 30-day crude and attributable mortality rates of candidemia patients were 44.7 and 19.6 %, respectively. Logistic regression analysis revealed significant independent predictors of mortality including admission to public sector hospital, APACHE II score at admission, underlying renal failure, central venous catheterization and steroid therapy.
Conclusion
The study highlighted a high burden of candidemia in Indian ICUs, early onset after ICU admission, higher risk despite less severe physiology score at admission and a vast spectrum of agents causing the disease with predominance of
C. tropicalis.
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